CDK9
cyclin dependent kinase 9, the group of Cyclin dependent kinases|P-TEFb complex subunits
Basic information
Region (hg38): 9:127785678-127790792
Previous symbols: [ "CDC2L4" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (5 variants)
- not provided (4 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDK9 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 7 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 1 | 1 | ||||
| non coding ? | 0 | |||||
| Total | 0 | 1 | 6 | 1 | 0 |
Highest pathogenic variant AF is 0.0000131
Variants in CDK9
This is a list of pathogenic ClinVar variants found in the CDK9 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 9-127785950-C-G | Bone mineral density quantitative trait locus 15 | association (Dec 01, 2009) | ||
| 9-127786219-A-G | not specified | Uncertain significance (Oct 06, 2021) | ||
| 9-127786780-G-C | not specified | Uncertain significance (Jan 23, 2024) | ||
| 9-127787511-C-T | CDK9-related disorder | Benign (Dec 31, 2019) | ||
| 9-127787515-C-T | CDK9-related disorder | Likely benign (Sep 28, 2023) | ||
| 9-127787532-C-A | CDK9-related disorder | Benign (Mar 29, 2019) | ||
| 9-127787999-C-T | CDK9-related disorder | Likely benign (Jan 05, 2023) | ||
| 9-127788008-C-T | CDK9-related disorder | Likely benign (Jun 24, 2019) | ||
| 9-127788034-T-C | CDK9-related disorder | Uncertain significance (Dec 27, 2023) | ||
| 9-127788049-T-G | Uncertain significance (Aug 17, 2022) | |||
| 9-127788066-G-A | not specified | Uncertain significance (Nov 07, 2022) | ||
| 9-127788208-C-T | CDK9-related disorder | Benign (Sep 11, 2019) | ||
| 9-127788283-T-A | not specified | Uncertain significance (Nov 08, 2022) | ||
| 9-127788595-T-C | CDK9-related disorder | Uncertain significance (Jan 03, 2024) | ||
| 9-127788612-C-T | not specified | Likely pathogenic (Mar 17, 2024) | ||
| 9-127788637-C-T | not specified | Uncertain significance (May 31, 2023) | ||
| 9-127789170-C-T | CDK9-related disorder | Likely benign (Feb 01, 2024) | ||
| 9-127789190-G-A | not specified | Uncertain significance (Jan 31, 2024) | ||
| 9-127789300-C-T | Likely benign (Oct 01, 2022) | |||
| 9-127789332-G-T | not specified | Uncertain significance (Nov 01, 2022) | ||
| 9-127789486-C-T | CDK9-related disorder | Likely benign (Nov 27, 2023) | ||
| 9-127789507-C-T | CDK9-related disorder | Likely benign (Feb 01, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CDK9 | protein_coding | protein_coding | ENST00000373264 | 7 | 5109 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0000889 | 0.939 | 125721 | 0 | 22 | 125743 | 0.0000875 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.14 | 145 | 238 | 0.609 | 0.0000149 | 2450 |
| Missense in Polyphen | 56 | 78.518 | 0.71321 | 852 | ||
| Synonymous | -2.27 | 126 | 97.5 | 1.29 | 0.00000633 | 713 |
| Loss of Function | 1.70 | 9 | 16.5 | 0.547 | 7.70e-7 | 189 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000210 | 0.000208 |
| Ashkenazi Jewish | 0.000413 | 0.000397 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000713 | 0.0000703 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000989 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Protein kinase involved in the regulation of transcription. Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to productive elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A, SUPT5H and RDBP. This complex is inactive when in the 7SK snRNP complex form. Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR, and the negative elongation factors DSIF and NELF. Regulates cytokine inducible transcription networks by facilitating promoter recognition of target transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-inducible STAT3 signaling). Promotes RNA synthesis in genetic programs for cell growth, differentiation and viral pathogenesis. P-TEFb is also involved in cotranscriptional histone modification, mRNA processing and mRNA export. Modulates a complex network of chromatin modifications including histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation (H3K4me3) and H3K36me3; integrates phosphorylation during transcription with chromatin modifications to control co-transcriptional histone mRNA processing. The CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II and can substitute for CDK9/cyclin-T P-TEFb in vitro. Replication stress response protein; the CDK9/cyclin-K complex is required for genome integrity maintenance, by promoting cell cycle recovery from replication arrest and limiting single- stranded DNA amount in response to replication stress, thus reducing the breakdown of stalled replication forks and avoiding DNA damage. In addition, probable function in DNA repair of isoform 2 via interaction with KU70/XRCC6. Promotes cardiac myocyte enlargement. RPB1/POLR2A phosphorylation on 'Ser-2' in CTD activates transcription. AR phosphorylation modulates AR transcription factor promoter selectivity and cell growth. DSIF and NELF phosphorylation promotes transcription by inhibiting their negative effect. The phosphorylation of MYOD1 enhances its transcriptional activity and thus promotes muscle differentiation. {ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10574912, ECO:0000269|PubMed:10757782, ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772, ECO:0000269|PubMed:11145967, ECO:0000269|PubMed:11575923, ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:11884399, ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:14701750, ECO:0000269|PubMed:15564463, ECO:0000269|PubMed:16109376, ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:17956865, ECO:0000269|PubMed:18362169, ECO:0000269|PubMed:19575011, ECO:0000269|PubMed:19844166, ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:20930849, ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:9857195}.;
- Disease
- DISEASE: Note=Chronic activation of CDK9 causes cardiac myocyte enlargement leading to cardiac hypertrophy, and confers predisposition to heart failure.;
- Pathway
- Transcriptional misregulation in cancer - Homo sapiens (human);MicroRNAs in cardiomyocyte hypertrophy;IL-9 Signaling Pathway;Cardiac Hypertrophic Response;Initiation of transcription and translation elongation at the HIV-1 LTR;Disease;Signal Transduction;Gene expression (Transcription);Formation of HIV-1 elongation complex containing HIV-1 Tat;Tat-mediated elongation of the HIV-1 transcript;HIV Transcription Elongation;HIV elongation arrest and recovery;Formation of HIV elongation complex in the absence of HIV Tat;Pausing and recovery of HIV elongation;Generic Transcription Pathway;Tat-mediated HIV elongation arrest and recovery;Pausing and recovery of Tat-mediated HIV elongation;Transcription of the HIV genome;Late Phase of HIV Life Cycle;HIV Life Cycle;Interactions of Tat with host cellular proteins;Host Interactions of HIV factors;HIV Infection;RNA Polymerase II Pre-transcription Events;Formation of RNA Pol II elongation complex ;RNA polymerase II transcribes snRNA genes;RNA Polymerase II Transcription;Infectious disease;RNA Polymerase II Transcription Elongation;SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription;AndrogenReceptor;IL-7 signaling;Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer;TP53 Regulates Transcription of DNA Repair Genes;JAK STAT pathway and regulation;EPO signaling;Signaling by Nuclear Receptors;Transcriptional Regulation by TP53;Estrogen-dependent gene expression;IL6;TNFalpha;Signaling by TGF-beta Receptor Complex;VEGF;Signaling by TGF-beta family members;ESR-mediated signaling
(Consensus)
Recessive Scores
- pRec
- 0.359
Intolerance Scores
- loftool
- 0.579
- rvis_EVS
- -0.58
- rvis_percentile_EVS
- 18.44
Haploinsufficiency Scores
- pHI
- 0.513
- hipred
- Y
- hipred_score
- 0.813
- ghis
- 0.627
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cdk9
- Phenotype
- integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hearing/vestibular/ear phenotype;
Zebrafish Information Network
- Gene name
- cdk9
- Affected structure
- hematopoietic multipotent progenitor cell
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- DNA repair;regulation of DNA repair;transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;transcription elongation from RNA polymerase II promoter;protein phosphorylation;regulation of mitotic cell cycle;cell population proliferation;positive regulation of cardiac muscle hypertrophy;regulation of histone modification;replication fork processing;positive regulation of transcription elongation from RNA polymerase II promoter;positive regulation of histone phosphorylation;response to drug;snRNA transcription by RNA polymerase II;positive regulation of transcription by RNA polymerase II;positive regulation of viral transcription;regulation of muscle cell differentiation;phosphorylation of RNA polymerase II C-terminal domain;negative regulation of cell cycle arrest;cellular response to cytokine stimulus;negative regulation of mRNA polyadenylation;positive regulation of mRNA 3'-UTR binding;positive regulation of histone H2B ubiquitination
- Cellular component
- cyclin-dependent protein kinase holoenzyme complex;nuclear chromatin;nucleus;nucleoplasm;chromosome;transcription elongation factor complex;cyclin/CDK positive transcription elongation factor complex;membrane;PML body;cytoplasmic ribonucleoprotein granule
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;transcription coactivator binding;DNA binding;chromatin binding;protein kinase activity;protein serine/threonine kinase activity;cyclin-dependent protein serine/threonine kinase activity;protein binding;ATP binding;transcription factor binding;RNA polymerase II CTD heptapeptide repeat kinase activity;kinase activity;protein kinase binding;cyclin binding;transcription regulatory region DNA binding;7SK snRNA binding